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Kashif Asghar,1 Shaarif Bashir,2 Iftikhar Ali Rana,2 Muhammad Abu Bakar,3 Asim Farooq,1 Muhammad Hassan,1 Zukhruf Asif,1 Mahnoor Afzal,1 Iqra Masood,4 Muhammad Ishaq,2 Muhammad Tahseen,2 Sundus Bilal,5 Shafqat Mehmood,5 Nosheen Kanwal,6 Islah Ud Din,6 Asif Loya2 1Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 2Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 3Department of Cancer Registry and Clinical Data Management, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 4Department of Clinical Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 5Department of Internal Medicine (Gastroenterology), Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, Pakistan; 6Department of Radiology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Punjab, PakistanCorrespondence: Kashif Asghar, Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre, 7-A Block R-3, Johar Town, Lahore, Punjab, 54000, Pakistan, Tel +92-42-35905000, Fax +92-42-35945206, Email kashifasghar@skm.org.pkBackground/Aim: Hepatocellular carcinoma (HCC) is one of the most common forms of liver cancer that is modulated by the immune system. Programmed cell death ligand-1 (PD-L1) has emerged as a novel therapeutic target in various cancers. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that is associated with poor prognoses in various cancer types. The aim of this study was to investigate the PD-L1 expression, and clinicopathological features of non-HCV and non-HBV-associated HCC patients, including IDO expression.Patients and Methods: In this study, immunohistochemical analysis was performed to analyze the expression of PD-L1 and IDO. Formalin-fixed paraffin-embedded HCC tumor tissues (n=50) were obtained from the pathology department, at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) in Lahore, Pakistan between 2005 and 2022. All the patients were HBV and HCV negative. Furthermore, it was a rare group of patients with no previous history of any viral hepatitis. In addition, for categorical and continuous variables chi-square or Fisher exact test and Mann–Whitney U-test was performed.Results: Of 50 tissue specimens, PD-L1+ was observed in 21 [high: 12 (24%), low: 9 (18%)] and PD-L1- was observed in 29 HCC patients. IDO+ was observed in all 50 specimens [high: 42 (84%), low: 8 (16%)]. Additionally, both PD-L1 and IDO had high expression in 11 (22%) patients. While both PD-L1 and IDO had low expression in 2 (4%) patients. Furthermore, in IDO+/PD-L1- group, 20 (69%) out of 29 patients died while in the IDO+/PD-L1+ group, 9 (43%) out of 21 patients died.Conclusion: Evaluation of IDO and PD-L1 expression may add therapeutic advantage in non-HCV and non-HBV-associated HCC patients that overexpress IDO. Further validation in a larger cohort is warranted.Keywords: programmed cell death ligand-1, indoleamine 2, 3-dioxygenase, non-HCV HCC, non-HBV HCC, immune checkpoint molecules

From pivotal roles in autonomous vehicles, healthcare diagnostics, and surveillance systems to seamlessly integrating with augmented reality, object detection algorithms stand as the cornerstone in unraveling the complexities of the visual world. Tracing the trajectory from conventional region-based methods to the latest neural network architectures reveals a technological renaissance where algorithms metamorphose into digital artisans. However, this journey is not without hurdles, prompting researchers to grapple with real-time detection, robustness in varied environments, and interpretability amidst the intricacies of deep learning. The allure of addressing issues such as occlusions, scale variations, and fine-grained categorization propels exploration into uncharted territories, beckoning the scholarly community to contribute to an ongoing saga of innovation and discovery. This research offers a comprehensive panorama, encapsulating the applications reshaping our digital reality, the advancements pushing the boundaries of perception, and the open issues extending an invitation to the next generation of visionaries to explore uncharted frontiers within object detection.

Technology entrepreneur new venture creation (TENVC) plays an important role in developing and commercializing technologies worldwide. Yet, one of the critical and on-going debates is about the paradigm shift from the trait approach to the behavioral approach which emerges from what successful entrepreneurs do and how they perform, rather than what their personality traits are. Therefore, the purpose of this research was to study both the entrepreneurial spirit and self-efficacy as key factors for TENVC. The mixed methods research was employed by combining the quantitative and qualitative approaches. The samples were chosen based on convenience sampling for the quantitative study and judgment sampling for the qualitative study. The finding shows that both entrepreneurial spirit and self-efficacy are correspondingly important for TENVC among technical students and Institutes of Higher Learning (IHLs). There is only a small difference in value in their positive significant relationship led by self-efficacy compared to entrepreneurial spirit with r=.005 for TENVC of technical students in IHLs. This finding is convergent with the outcome of the case study analysis that both factors are among the key indicators for TENVC of technical students in IHLs. The technology entrepreneur development organizations (TEDO) may utilize this result in developing TENVC in their institutions.

Mining activities contribute the high level of air pollution at ground level and have significant environmental impacts. There is an urge to develop an integrated modeling system which helps to analyze these pollutants and their control strategies. Therefore, a new integrated approach is conceptualized as life cycle based air quality modeling system (LCAQMS) for the mining. This paper focuses on incorporating air quality modeling to understand the severity of air pollution in mining and developing an integrated system for mining related decision support with a field application. The system integrates inverse matrix which is used to develop air emission inventory; characterization method to assess the environmental implications; artificial neural network model for carbon footprint analysis; air dispersion modeling to predict the pollutant concentration at receptor level; and multicriteria decision analysis tool to provide air pollution control solutions. The developed LCAQMS method has applied to a copper mining site in the US. Inventory results reveal that NOX and SO2 produced more as compared to the other pollutants for this site. The study also helps to quantify the carbon credits for the copper mine. Prediction of the four significant pollutants (PM10, PM2.5, SO2, NOx) at ground level have been further calculated and validated with observed values at seven different monitoring stations. The modeling results have supported selecting the best alternative management technology for the air pollution control. It indicates that the developed LCAQMS can serve as a useful tool to assess, predict and assist in the selection of environmental mitigation options for mining sites. [ABSTRACT FROM AUTHOR]

CX-5461 recently progressed through phase I clinical trial as a first-inhuman inhibitor of RNA-POL I. Here, the authors demonstrate that CX-5461 synergizes with topoisomerase I inhibitors to inhibit neuroblastoma cells and that its primary target in this disease is topoisomerase II beta and not RNA-POL I.

Background A recent government white paper sets out proposals for reforms to the Mental Health Act 1983 (MHA). Some of these proposals affect people with intellectual disabilities and/or autism. Aims To explore both positive and unintended negative effects of the proposed reforms by gathering the perspectives of healthcare workers from multiple disciplines, working with intellectual disability and/or autism in community and in-patient settings. Method A 14-question electronic questionnaire, comprising free-text, multiple choice and five-point Likert scale responses, was sent out via email between April and July 2021, to all multidisciplinary team professionals working in specialist intellectual disability community and in-patient teams in Hertfordshire Partnership University NHS Foundation Trust. Results There were 45 responders, of whom 53% worked in in-patient settings and 47% in out-patient teams. Respondents comprised healthcare professionals from multiple disciplines, 80% of which were non-medical. Most responders agreed with the general principles of the proposed reforms. However, 80% felt there would be potentially unintended consequences, and 76% thought that substantial investment in community services was required in advance of the proposed reforms. Conclusions The proposed MHA reforms may have unintended consequences for people with intellectual disabilities and/or autism. The findings of this study raised key concerns that need to be explored further and addressed before the MHA reforms are implemented. These include community provision, safeguards and use of the Mental Capacity Act, the potential for under or overdiagnosis of mental illness, and effects associated with the criminal justice system.

Formation damage in oil reservoirs because of fines migration is among the main contributors to productivity decline. Conventionally, chemical methods such as complex organic polymers are used to prevent fines migration by stabilizing or maintain the fines particles in aggregated form. However, most of the chemical fines stabilizer is not robust, which functionalize based on the composition of exchangeable cations in clay minerals, temporary stabilization and are not environmentally friendly. In this research work, qualitative methods were developed to investigate the potential of Magnesium Oxide (MgO) and Silica Dioxide (SiO2) Nano-Fluids addition with surfactants (Triton X-100 and Tween 80) as a new technique to control fines migration. Silicon Dioxide nanoparticles used in this experiment are in the form of colloidal silica with spherically sized at 10-15 nm then stabilized electrostatically to allow the particles to stay suspended in the solution. To measure the Nano-Fluids and fines solution stability, the minerals (kaolinite, bentonite and illite-smectite) crushed and suspended in 100 mL distilled water with 0.20%, 0.50%, 1.50% and 3% concentration, respectively. The suspended fines solutions left for 24 hours. Solution stability measured using the Zetasizer Nano ZSP by recording their turbidity (NTU) and zeta potential (mV). The results from the assessment shown that bentonite and kaolinite fines are more susceptible to migration in sandstone reservoirs due to their high colloidal stability from their zeta potential measurements and their morphologies. It can also be concluded that Silicon Dioxide (SiO2) is more stable when these nanoparticles are suspended in de-ionized water only, which gives zeta potential values of -26.10 mV. The addition of surfactants (Triton X-100 and Tween 80) has also shown significant results on protected fines migration. Triton X-100 and Tween 80 increased Silicon Dioxide (SiO2) Nano-fluid zeta potential value at -30.6 mV, which is beneficial for the Nano-Fluid to travel deeper into the formation to treat problematic areas of fines migration.

Background Attention-deficit hyperactivity disorder (ADHD) is common among people with intellectual disability. Diagnosing ADHD in this clinically and cognitively complex and diverse group is difficult, given the overlapping psychiatric and behavioural presentations. Underdiagnoses and misdiagnoses leading to irrational polypharmacy and worse health and social outcomes are common. Diagnostic interviews exist, but are cumbersome and not in regular clinical use. Aims We aimed to develop a screening tool to help identify people with intellectual disability and ADHD. Method A prospective cross-sectional study, using STROBE guidance, invited all carers of people with intellectual disability aged 18–50 years open to the review of the psychiatric team in a single UK intellectual disability service (catchment population: 150 000). A ten-item questionnaire based on the DSM-V ADHD criteria was circulated. All respondents’ baseline clinical characteristics were recorded, and the DIVA-5-ID was administered blinded to the individual questionnaire result. Fisher exact and multiple logistic regressions were conducted to identify relevant questionnaire items and the combinations that afforded best sensitivity and specificity for predicting ADHD. Results Of 78 people invited, 39 responded (26 men, 13 women), of whom 30 had moderate-to-profound intellectual disability and 38 had associated comorbidities and on were medication, including 22 on psychotropics. Thirty-six screened positive for ADHD, and 24 were diagnosed (16 men, eight women). Analysis showed two positive responses on three specific questions to have 88% sensitivity and 87% specificity, and be the best predictor of ADHD. Conclusions The three-question screening is an important development for identifying ADHD in people with intellectual disability. It needs larger-scale replication to generate generalisable results.

In this work, a simple gold-glazed dual-core photonic crystal fiber (PCF) is inspected by using surface plasmon resonance for biochemical sensing. Based on high sensing performance and chemical substantiality, gold (Au) is selected as plasmonic material to coat the external surface of the design. The target analyte and gold layer are placed on the outer surface of the PCF to offer fabrication simplicity. A central elliptical air hole is embellished to increase structural asymmetry between both cores hence the sensor came out with improved sensing performances. The numerical analysis of the proposed design is investigated employing the finite element method (FEM). The maximum optimized value of wavelength sensitivity is recorded at about 8000 nm/RIU with a resolution of 12.5×10−6 and amplitude sensitivity is achieved 1443 RIU−1 for the refractive index of 1.39. Furthermore, a detailed study is also performed to investigate the effects of varying sensor's geometrical parameters such as the thickness of gold and analyte layer, pitch distance, diameters of cladding air holes, geometrical shapes of air hole at core. According to these results along with simple structural design, the proposed model can be practical enough for biochemical and bio-molecular substance detection.

Abstract Background The gap gene system controls the early cascade of the segmentation pathway in Drosophila melanogaster as well as other insects. Owing to its tractability and key role in embryo patterning, this system has been the focus for both computational modelers and experimentalists. The gap gene expression dynamics can be considered strictly as a one-dimensional process and modeled as a system of reaction-diffusion equations. While substantial progress has been made in modeling this phenomenon, there still remains a deficit of approaches to evaluate competing hypotheses. Most of the model development has happened in isolation and there has been little attempt to compare candidate models. Results The Bayesian framework offers a means of doing formal model evaluation. Here, we demonstrate how this framework can be used to compare different models of gene expression. We focus on the Papatsenko-Levine formalism, which exploits a fractional occupancy based approach to incorporate activation of the gap genes by the maternal genes and cross-regulation by the gap genes themselves. The Bayesian approach provides insight about relationship between system parameters. In the regulatory pathway of segmentation, the parameters for number of binding sites and binding affinity have a negative correlation. The model selection analysis supports a stronger binding affinity for Bicoid compared to other regulatory edges, as shown by a larger posterior mean. The procedure doesn’t show support for activation of Kruppel by Bicoid. Conclusions We provide an efficient solver for the general representation of the Papatsenko-Levine model. We also demonstrate the utility of Bayes factor for evaluating candidate models for spatial pattering models. In addition, by using the parallel tempering sampler, the convergence of Markov chains can be remarkably improved and robust estimates of Bayes factors obtained.

OBJECTIVE: Tо evaluate the bacterial sensitivity pattern іn nеоnаtаl ѕерѕіѕ at Neonatal Unit, Civil Hospital Hyderabad. METHODOLOGY: The observational Cross-sectional study was conducted at Neonatal Unit, Dераrtmеnt оf Раеdіаtrіϲѕ, Civil Hоѕріtаl, Hуdеrаbаd from 1st January to 30th June 2014. Total 332 Nеоnаtеѕ (1 – 28 dауѕ оf lіfе) ԝіth neonatal sepsis were included in this study. Nеоnаtеѕ ԝhо had аlrеаdу rеϲеіvеd аntіbіоtіϲѕ аnd ԝіth grоѕѕ ϲоngеnіtаl mаlfоrmаtіоn ԝеrе еxϲludеd frоm thе ѕtudу. Аll nеоnаtеѕ ԝhо mееt thе іnϲluѕіоn ϲrіtеrіа were investigated (ϲоmрlеtе blооd ϲоunt, рrоthrоmbіn tіmе, & Blооd ϲulturеѕ). Positive Blood cultures were evaluated for their sensitivity to various antibiotics. RЕЅULTЅ: Thе mеаn аgе ԝаѕ 17.3±7 dауѕ, 181 (54.5%) ԝеrе mаlе аnd 151 (46.4%) ԝеrе fеmаlе, 200 (76.6%) ԝеrе ϲаѕеѕ оf еаrlу оnѕеt nеоnаtаl ѕерѕіѕ аnd 132 (66.2%) ԝеrе lаtе оnѕеt ѕерѕіѕ. History of Рrеmаturе ruрturе оf mеmbrаnе was present in 24.6%. Klеbѕіеllа рnеumоnіае ԝаѕ thе mоѕt ϲоmmоn оrgаnіѕm іѕоlаtеd frоm blооd (39.78%) fоllоԝеd bу Е. ϲоlі (22.58%) аnd ѕtарhуlоϲоϲϲuѕ аurеuѕ (18.27%).Klebsiella was sensitive to Amikacin, Gentamycin and Ciprofloxacin in 100% cases, while it was resistant to Ampicillin in 100% cases. CОNCLUЅІОNЅ: Іt іѕ ϲоnϲludеd frоm thіѕ ѕtudу thаt Klеbѕіеllа ԝаѕ thе mоѕt ϲоmmоn оrgаnіѕm fоr nеоnаtаl ѕерѕіѕ and it was ѕеnѕіtіvе tо ϲоmmоn аntіbіоtіϲѕ.

The relative importance of the key determinants of agricultural-production by performing sensitivity analysis on a cross country dataset of 81 countries has been investigated. For analyzing the significance of regional differences in agricultural production, two dummy variables were used for high and low income countries. The World Bank dataset is used for this study ranging from 2002 to 2013 and cross-country regression coefficients are estimated through the ordinary least square method. The study finds the role of land, physical capital, human capital and fertilizer as positive and statistically significant in agricultural-production. The study further finds that physical-capital contributes more consistently than human capital does in agri-production. However, the presence of physical-capital in agricultural-production leads to the creation of a disguised unemployment in the agricultural sector, which should be channelized in order to attain maximum production. The regional dummies for low and high-income countries are found to be statistically significant. The results show that agriculture production, given the inputs, is higher in high-income countries and lower in low income countries. [ABSTRACT FROM AUTHOR]

In this work, we report the results of the compositional analysis of an aluminum gallium arsenide (AlGaAs) sample using the calibration-free laser-induced breakdown spectroscopy (CF-LIBS) technique. The AlGaAs sample was doped with three various concentrations of gallium (Ga), arsenic (As), and aluminum (Al), as reported by the manufacturer, and the CF-LIBS technique was employed to identify the doping concentration. A pulsed Q-switched Nd: YAG laser capable of delivering 200 and 400 mJ energy at 532 and 1064 nm, respectively, was focused on the target sample for ablation, and the resulting emission spectra were captured using a LIBS 2000+ spectrometer covering the spectral range from 200 to 720 nm. The emission spectra of the AlGaAs sample yielded spectral lines of Ga, As, and Al. These lines were further used to calculate the plasma parameters, including electron temperature and electron number density. The Boltzmann plot method was used to calculate the electron temperature, and the average electron temperature was found to be 5744 ± 500 K. Furthermore, the electron number density was calculated from the Stark-broadened line profile method, and the average number density was calculated to be 6.5 × 1017 cm−3. It is further observed that the plasma parameters including electron temperature and electron number density have an increasing trend with laser irradiance and a decreasing trend along the plume length up to 2 mm. Finally, the elemental concentrations in terms of weight percentage using the CF-LIBS method were calculated to be Ga: 94%, Al: 4.77% and As: 1.23% for sample-1; Ga: 95.63%, Al: 1.15% and As: 3.22% for sample-2; and Ga: 97.32%, Al: 0.69% and As: 1.99% for sample-3. The certified concentrations were Ga: 95%, Al: 3% and As: 2% for sample-1; Ga: 96.05%, Al: 1% and As: 2.95% for sample-2; and Ga: 97.32%, Al: 0.69% and As: 1.99% for sample-3. The concentrations measured by CF-LIBS showed good agreement with the certified values reported by the manufacturer. These findings suggest that the CF-LIBS technique opens up an avenue for the industrial application of LIBS, where quantitative/qualitative analysis of the material is highly desirable.

Nowadays, the management and analyses of `big data' are becoming indispensable for numerous organizations all over the world. In many cases, multiple organizations want to perform data analyses on their combined databases. Skyline query is one of the popular operations for selecting representative objects from a large database, where any other object within the database does not dominate each of the representative objects, called `skyline'. Like other data analytics operations, the multi-party skyline query can provide benefits to the participating organizations by retrieving the skyline objects from their combined databases. Such a multi-party skyline query demands the disclosure of individual parties' objects to others during the computation. But, owing to the data privacy and security concern of the present IT era, such disclosure of the individual parties' databases is strictly prohibited. Considering this issue, we are proposing a new framework for the privacy-preserving multi-party skyline query, exploiting additive homomorphic encryption along with data anonymization, perturbation, and randomization techniques. The underlying protocols within our proposed framework ensure that every participating party can identify its multi-party skyline objects without revealing the objects to others during the multi-party skyline query. The detailed privacy and security analyses show that the proposed framework can achieve the desired computation goal without privacy leakage. Besides, the performance evaluation through complexity analyses, extensive simulations, and comprehensive comparison also demonstrate the utility and the efficiency of the proposed framework.